Mr1-KO Mouse

MR1, the MHC class I-related protein 1, is a non-classical class I molecule highly conserved among mammals [1]. It presents non-peptidic small molecules, like those from the riboflavin biosynthesis pathway, to MR1-restricted T cells. Since mammals don't synthesize riboflavin, MR1 can act as a sensor of the microbial metabolome, being crucial for early detection of intracellular infection [1]. It also plays a role in MHC antigen presentation, fundamental to adaptive and semi-invariant T cell immunity [2].

MR1-restricted T cells, including mucosal-associated invariant T (MAIT) cells, can recognize MR1-presented antigens. These T cells have diverse functions in different biological contexts. In cancer, while MAIT cells may augment cancer growth and metastases, other MR1-restricted T cells can recognize and kill a variety of MR1-expressing tumor cells, suggesting potential for cancer immunotherapy [3,4,6]. In Mycobacterium tuberculosis infection, MR1 presents small microbial metabolites to a distinct subset of CD8+ T cells [5]. Also, the MR1/MAIT cell axis has been investigated in CNS diseases like multiple sclerosis, brain cancer, and Alzheimer's disease, highlighting its role in neuropathology [7].

In conclusion, MR1 is essential for presenting small molecule antigens to T cells, playing a key role in immune surveillance against infections and potentially in cancer immunity. The study of MR1-restricted T cells in various disease models, such as in cancer and CNS diseases, provides insights into its functions and potential therapeutic applications.

References:

1. Karamooz, Elham, Harriff, Melanie J, Lewinsohn, David M. . MR1-dependent antigen presentation. In Seminars in cell & developmental biology, 84, 58-64. doi:10.1016/j.semcdb.2017.11.028. https://pubmed.ncbi.nlm.nih.gov/30449535/

2. McWilliam, Hamish E G, Villadangos, Jose A. 2023. MR1 antigen presentation to MAIT cells and other MR1-restricted T cells. In Nature reviews. Immunology, 24, 178-192. doi:10.1038/s41577-023-00934-1. https://pubmed.ncbi.nlm.nih.gov/37773272/

3. Vacchini, Alessandro, Chancellor, Andrew, Spagnuolo, Julian, Mori, Lucia, De Libero, Gennaro. 2020. MR1-Restricted T Cells Are Unprecedented Cancer Fighters. In Frontiers in immunology, 11, 751. doi:10.3389/fimmu.2020.00751. https://pubmed.ncbi.nlm.nih.gov/32411144/

4. Flores-Villanueva, Pedro, Sobhani, Navid, Wang, Xu, Li, Yong. 2020. MR1-Restricted T Cells in Cancer Immunotherapy. In Cancers, 12, . doi:10.3390/cancers12082145. https://pubmed.ncbi.nlm.nih.gov/32756356/

5. Kim, Se-Jin, Karamooz, Elham. 2022. MR1- and HLA-E-Dependent Antigen Presentation of Mycobacterium tuberculosis. In International journal of molecular sciences, 23, . doi:10.3390/ijms232214412. https://pubmed.ncbi.nlm.nih.gov/36430890/

6. Wang, Zhiding, Wang, Mengzhen, Chen, Jinghong, Zhang, Li, Yu, Li. . MR1-restricted T cells: the new dawn of cancer immunotherapy. In Bioscience reports, 40, . doi:10.1042/BSR20202962. https://pubmed.ncbi.nlm.nih.gov/33185693/

7. Shrinivasan, Rashmi, Wyatt-Johnson, Season K, Brutkiewicz, Randy R. 2023. The MR1/MAIT cell axis in CNS diseases. In Brain, behavior, and immunity, 116, 321-328. doi:10.1016/j.bbi.2023.12.029. https://pubmed.ncbi.nlm.nih.gov/38157945/